Nucleophosmin/B23 regulates transcriptional activation of E2F1 via modulating the promoter binding of NF-κB, E2F1 and pRB

Chiao Yun Lin, Yu Chun Liang, Yat Ming Yung

Research output: Journal article publicationJournal articleAcademic researchpeer-review

27 Citations (Scopus)

Abstract

Expression of nucleophosmin/B23 and E2F1 and E2F1-dependent transcription increased in U1 bladder cancer cells upon serum stimulation from quiescence. Nucleophosmin/B23-siRNA treatment abrogated such increase of E2F1-dependent transcriptional activity. In identifying physiologically important factors that may occupy E2F1 promoter and regulate its activity in vivo, we found that the pattern of NF-κB, E2F1 and pRB recruitment to E2F1 promoter changed in a strikingly dynamic fashion as cells progressed from quiescence into serum-stimulated growth. E2F1 promoter activity in quiescent cells was associated with recruitment of NF-κB. NF-κB was replaced largely by E2F1 in concert with gene activation during the early stage (12 h) of serum stimulation. At late stage (24 h) of serum stimulation, pRB was then recruited to the E2F1-promoter complex to counterbalance its activity. Upon siRNA-mediated reduction of intracellular nucleophosmin/B23, E2F1 and pRB were recruited to the promoter with the dissociation of NF-κB concomitant with gene inactivation. Based on immunoprecipitation experiments, nucleophosmin/B23 was found to be associated with NF-κB in cells grown in serum-supplemented but not in serum-deprived medium. Furthermore, nucleophosmin/B23 could also be co-immunoprecipitated with ppRB at the early stage (12 h) but not at the late stage (24 h) of serum stimulation. The results demonstrate a novel mechanism for transcriptional regulation of E2F1 and identify the functional role of nucleophosmin/B23 in modulating the binding of NF-κB, E2F1 and pRB to activate E2F1 promoter.
Original languageEnglish
Pages (from-to)2041-2048
Number of pages8
JournalCellular Signalling
Volume18
Issue number11
DOIs
Publication statusPublished - 1 Nov 2006
Externally publishedYes

Keywords

  • E2F1
  • Nucleophosmin/B23
  • Transcriptional regulation

ASJC Scopus subject areas

  • Cell Biology

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